genetic polymorphism

Steroids are the primary treatment for idiopathic nephrotic syndrome. Pharmacogenomic factors, including genetic and histological modifications, play a significant role in influencing the response to steroids. One such factor is the excessive synthesis of P-glycoprotein (permeability glycoprotein) and multidrug resistance-associated protein 1 (MDR-1), which may contribute to the development of steroid resistance and alterations in steroid pharmacokinetics.

We examined the correlation between steroid responsiveness and the MDR-1 gene variations, specifically rs1045642 (3435T/C) and rs2032582 (2677G/T/A), in children in Iraq diagnosed with idiopathic nephrotic syndrome (INS).

In this cross-sectional study, one hundred Iraqi pediatric patients aged one to 16 years, all diagnosed with primary nephrotic syndrome and treated with prednisolone, were enrolled. After isolating genomic DNA, genotyping was performed using the allele-specific polymerase chain reaction (PCR) technique. A notable correlation was identified between the adenosine triphosphate-binding cassette B1 (ABCB1) gene SNPs 3435T>C and 2677G>T/A, and the likelihood of prednisolone resistance in these patients with nephrotic syndrome.

The study included 45 cases of steroid-sensitive nephrotic syndrome (SSNS), 38 cases of steroid-dependent nephrotic syndrome (SDNS), and 17 cases of steroid-resistant nephrotic syndrome (SRNS). Our investigation revealed a significant correlation between the 3435T>C polymorphism of the ABCB1 gene and the likelihood of resistance to prednisolone in pediatric patients with nephrotic syndrome (p = 0.02). The genotype distribution for rs1045642 (3435T>C SNP) was 14 TT, 68 TC, and 18 CC. For rs2032582 (2677G/T/A SNP), the genotype distribution was 18 GG, 16 GT, 24 TT, 23 TA, and 19 AA. Additionally, the 2677G>T/A polymorphism was significantly associated with the onset of prednisolone-resistant nephrotic syndrome (P = 0.043).

This study concluded that children with the MDR-1 3435T/C and 2677G/T/A polymorphisms may be more vulnerable to SRNS and, therefore, may require alternative therapeutic approaches.

This study aims to investigate how genetic variations in genes essential for spermatogenesis may influence the risk of male infertility. Specifically, it focuses on the HTR2A and SLC18A genes, which are involved in selective serotonin reuptake and may affect sperm differentiation, maturation, and motility. The primary objective was to evaluate the association between the rs6313 and rs2270641 polymorphisms in these genes and infertility among men attending the infertility center at Beheshti Hospital in Kashan.
A case-control study design was utilized, involving 110 men diagnosed with infertility and 120 healthy controls. Semen samples were collected from all participants, followed by genomic DNA extraction. Polymerase chain reaction (PCR) was employed to amplify the DNA, and genotyping for the rs6313 and rs2270641 polymorphisms was performed using PCR-restriction fragment length polymorphism (RFLP) analysis. Statistical comparisons of genotype and allele frequencies between the infertile and control groups were conducted using the chi-square test.
The analysis revealed a statistically significant association between the rs2270641 polymorphism in the SLC18A gene and male infertility. Notably, the GG genotype was more prevalent in the infertile group compared to the control group (P = 0.04). Furthermore, the presence of the G allele was associated with an increased risk of infertility (odds ratio [OR] = 1.4854, 95% confidence interval [CI] = 1.0282 to 2.1459, P = 0.035). Conversely, no significant association was identified between the rs6313 polymorphism and male infertility risk.
The findings suggest that the rs2270641 polymorphism may serve as a molecular marker for heightened susceptibility to male infertility. However, additional research involving larger sample sizes and diverse ethnic populations is warranted to confirm and refine these results.

Congenital heart defects (CHD) are recognized as the most common heart abnormalities amongst newborns and children, and atrial septal defect (ASD) is recognized as one of the most frequent forms of CHD. Prior studies indicated that the methylenetetrahydrofolate reductase (MTHFR) gene contributes to the etiology of CHD. Therefore, we designed a case-control study to assess the possible role of the MTHFR gene, specifically the C677T (rs1801133) and A1298C (rs1801131) polymorphisms within the Iranian ASD population sample.

A total of 166 subjects (81 children diagnosed with ASD and 85 control participants) were enrolled in this research. Samples genotyped for MTHFR rs1801133 and rs1801131 polymorphisms using the PCR-RFLP and ARMS-PCR approaches.

Our results indicated that rs1801131 variant reduced the risk of ASD in codominant (OR [95%CI]: 0.41[0.21-0.83], P=0.012), dominant (OR[95%CI]: 0.48 [0.25-0.93], p=0.028) and overdominant (OR[95%CI]: 0.44 [0.23-0.81], P=0.009) models. Moreover, rs1801133 variant increased the risk of ASD in codominant (OR[95%CI]: 2.68[1.39-5.16], P = 0.003), dominant (OR [95% CI]: 2.72 [1.43–5.14], P = 0.002), overdominant (OR [95% CI]: 2.50 [1.31–4.78], P = 0.005), and allelic (OR [95% CI]: 2.16 [1.27–3.69], P = 0.004) models.

Our findings suggest that MTHFR rs1801133 and rs1801131 variants may potentially affect the onset of ASD.

The relationship between vitamin D receptor (VDR). Polymorphisms, and diabetes remain uncertain. This study aimed to examine the potential correlation between type 2 diabetes mellitus (T2DM) and rs739837 single nucleotide polymorphism (SNP) in the Mazandaran province population.

A case-control study was conducted, involving 100 individuals diagnosed with T2DM and 100 healthy controls, all residents of Mazandaran province. The extraction of genomic DNA and rs739837 polymorphism was genotyped using the Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) method.

The data indicated a significant association between GT genotype and a decreased risk of T2DM (OR= 0.5135, 95%CI= 0.2759 to 0.9559, P=0.0355). Moreover, individuals carrying T allele showed a reduced likelihood of progressing T2DM (OR= 0.4657, 95%CI= 0.2564 to 0.8461, P=0.0121).

The findings suggested that rs739837 polymorphism in the VDR gene may serve as a protective factor against T2DM in the studied population. Further research with larger samples is needed to confirm these results across different populations.

 Obesity is a multifactorial disorder that has considerably increased in developing countries in recent years. This disease results from an imbalance between energy intake and expenditure, influenced by various factors such as behavior, diet, environment, metabolic factors, and genetics. Different genetic aspects of obesity seek mutations in genes that are responsible for appetite control and metabolism. FNDC5 is a glycosylated membrane protein that is highly expressed in the heart, brain, and skeletal muscle tissues in mice. This protein is cleaved by an unknown protease at the cell surface. This study aimed to investigate the rs1746661 polymorphism in the FNDC5 gene among obese patients.

 The blood samples were collected from 100 individuals visiting Shariati Hospital in Isfahan and the Social Security Clinic for DNA extraction using the phenol-chloroform method, and informed consent was obtained from them for their participation in the study. Specific primers for G/A/T alleles were designed for the amplification refractory mutation system-polymerase chain reaction (PCR) method, and PCR was performed. The results were examined on agarose gel electrophoresis and statistically analyzed using SPSS 22 software.

 Based on genetic analysis investigations, our findings revealed a significant association between the GT genotype in the rs1746661 polymorphism and the occurrence of obesity and/or other metabolic disorders. Such genotypes can be considered predisposing polymorphisms for obesity and/or other metabolic problems.

 Overall, the multifactorial nature of obesity, such as lifestyle and dietary habits, should receive special attention.

Anxiety disorders (ADs) are a group of mental disorders characterized by feelings of tension, fear, and excessive worrying in the face of life experiences. Aberrant signaling of adenosine A2a receptor (ADORA2A) is believed to be involved in the pathogenesis of ADs. Polymorphisms in the ADORA2A gene were shown to be associated with some of the patterns presented by ADs. The results of these studies have been inconsistent, making it hard to draw definitive conclusions. Therefore, this study performed a systematic review to clarify the associations between ADORA2A gene polymorphisms and ADs susceptibility. PubMed/Medline, Web of Science, and Scopus database using appropriate keywords, then screened for separation of suitable studies based on inclusion/exclusion criteria. Collectively, rs5751876 (1976T>C or previously 1083C>T) and rs35060421 (2592C>Tins) polymorphisms of ADORA2A were associated with an increased susceptibility to ADs. Moreover, rs2298383 TT genotype may be the causal regulatory factor, and ADORA2A T/C (rs2298383/rs3761422) haplotypes have significant susceptibility to ADs development. Additional research is needed to further define the role of ADORA2A gene polymorphisms in the pathogenesis of ADs.

Endometriosis is a chronic, gynecological disorder, and the disease's pathogenesis is still debatable. Genes related to apoptosis have been revealed to be deregulated in endometriosis.

This study investigates the relationship between polymorphic variants of Bax -248G>A and Bcl-2 -938C>A promoter regions with endometriosis risk in an Iranian population.

In this case-control study, the polymorphisms of Bax -248G>A and Bcl-2 -938C>A promoter regions were analyzed in 127 Iranian cases and 125 controls who were referred to Ali-ibn-Abi Taleb Educational hospital, Zahedan, Iran between May 2022 and February 2023. The genotypic analysis was performed for all the subjects using the polymerase chain reaction-restriction fragment length polymorphism method.

The frequencies of mutant allele A carriers and the A allele of Bax -248G>A polymorphism showed about 2-fold significant increase of endometriosis risk (p = 0.04; p = 0.01, respectively). The frequencies of the mutant genotype AA and A allele carriers of Bcl-2 -938C>A polymorphism were approximately 4 and 2.5-fold higher in endometriosis compared to the control women, which were highly significant (p > 0.001). Moreover, the allele A frequency of Bcl-2 -938C>A was associated with a 2-fold higher risk of endometriosis (p > 0.001). Furthermore, the combination effects of these 2 single nucleotide polymorphisms showed that women with Bax -248G>A GG and Bcl-2 -938C>A AA variant alleles were associated with about 5 times higher risk of endometriosis (p > 0.001). Notably, a significant difference was observed in mutant allele distribution between minimal/mild (stage I and II) and moderate/severe (stage III and IV) women with endometriosis disease.

The results of our study provide evidence that Bcl-2 -938C>A and Bax -248G>A single nucleotide polymorphisms might be associated with the risk of endometriosis.

Host genetic changes like single nucleotide polymorphisms (SNPs) are one of the main fac- tors influencing susceptibility to viral infectious diseases. This study aimed to investigate the association between the host SNP of Toll-Like Receptor3 (TLR3) and Toll-Like Receptor7 (TLR7) genes involved in the immune system and susceptibil- ity to COVID-19 in a sample of the Iranian population.

This retrospective case-control study evaluated 244 hospitalized COVID-19 patients as the case group and 156 suspected COVID-19 patients with mild signs as the control group. The genomic DNA of patients was gen- otyped for TLR7 (rs179008 and rs179009) and TLR3 (rs3775291 and rs3775296) SNPs using the polymerase chain reac- tion-restriction fragment length polymorphism (PCR-RFLP) method.

A significant association between rs179008 SNP in the TLR7 gene and the susceptibility of COVID-19 was found between case and control groups. The AT genotype (Heterozygous) of TLR7 rs179008 A>T polymorphism showed a sig- nificant association with a 2.261-fold increased odds of COVID-19 (P=0.003; adjusted OR: 2.261; 99% CI: 1.117-4.575). In addition, a significant association between TC genotype of TLR7 rs179009 T>C polymorphism and increased odds of COVID-19 (P< 0.0001; adjusted OR: 6.818; 99% CI: 3.149-14.134) were determined. The polymorphism frequency of TLR3 rs3775291 and rs3775296 genotypes were not significantly different between the case and control groups (P> 0.004167).

SNPs in TLR7 rs179008 and rs179009 genotypes are considered host genetic factors that could be influenced individual susceptibility to COVID-19. The SNPs in TLR3 (rs3775296 and rs3775291) showed no significant association with COVID-19 in Iranian population.

 Early immune responses to COVID-19 can help eliminate the virus; therefore, strategies to improve the immune system have become important in disease prevention. Vitamin D plays a crucial role in the immune response to SARS-CoV-2 by increasing the expression of the vitamin D receptor.

 This study investigated the impact of vitamin D deficiency, Fok 1, and Taq 1 Vitamin D Receptor (VDR) gene polymorphisms and comorbidities on the susceptibility to COVID-19.

 Fok1 and Taq1 polymorphisms were analyzed using the RT-PCR method, and vitamin D levels were measured using the chemiluminescence method. A total of 200 patients, 100 with COVID-19 and 100 without, provided blood samples for analysis.

 The COVID-19 positive group had a significantly lower mean vitamin D level of 16.2 ± 11.3 ng/mL compared to the COVID-19 negative control group, 26.7 ± 15.9 ng/mL (P < 0.001). Individuals with a vitamin D level below 18.4 ng/mL had a 2.448 times higher risk of COVID-19 positivity (P < 0.001). There was no significant difference in the Fok1 and Taq1 gene polymorphisms between the two groups. (P = 0.548 and P = 0.098). The COVID-19 positive group had a significantly higher number of comorbid diseases with 40 (40%) compared to the negative group with 10 (10%) participants (P < 0.001).

 Levels of vitamin D above the cut-off value of 18.4 ng/mL were found to protect against COVID-19, while the presence of comorbid diseases was identified as a risk factor. However, no association was observed between the Fok1 and Taq1 polymorphisms and susceptibility to COVID-19.

Genetic polymorphisms are predictors of the immune response and susceptibility to certain infectious diseases, including pulmonary tuberculosis (TB). We evaluated the association of monocyte chemoattractant protein-1 (MCP1) (-2581 A/G) and interferon-gamma (IFNγ) (+874 T/A) polymorphisms with susceptibility to pulmonary TB in an Iranian population.

A total of 124 patients with pulmonary tuberculosis and 244 healthy subjects (121 related normal controls and 123 unrelated subjects) were included. The MCP1 polymorphic region (-2518 A/G) was genotyped by PCR-RFLP, while ARMS-PCR was used to amplify and detect IFNγ (+874 T/A). SNPStats and SPSS v. 20 were used for the statistical analysis of the data.

The comparison of MCP1 (-2518 A/G) alleles and genotypes in TB patients and healthy subjects showed no significant association in all the constructed heredity models. No association was observed between TB patients and normal subjects in all the constructed inheritance models for IFNγ (+874 T/A) alleles and genotypes.

Due to the lack of association between MCP1 (-2518 A/G) and IFNγ (874 T/A) polymorphisms and susceptibility to PT in our study and the conflicting results of some previous studies, further clinical and molecular research is needed to clarify the role of the studied polymorphisms in the pathogenesis of tuberculosis.

Rotator Cuff Tear (RCT) is a multifactorial disease, but an important one is the increased collagen degradation that would lead to a higher chance of tear. MMP-8 is a protein that degrades type I collagen, and it is known that MMP-8 has a polymorphism in which a T allele in the gene promoter region increases its transcription activity. This study aims to investigate the association between MMP -8 polymorphism g.-799 C>T (rs11225394) and RCT. To do that, we collected DNA samples from buccal epithelial cells of 128 patients (separated into RCT group and control group in a proportion 1:1) and genotyped the DNA using PCR. The statistical analyses were done using the ARLEQUIN Version 2.0, and the data normality was tested with the Shapiro-Wilk test. The results showed a significantly higher frequency of T/T genotype in the test group (29% in the control group and 39% in the test group, p=0.0417), and that would represent a risk factor for increased collagen degradation. The MMP-8 g.-799 C>T (rs11225394) SNP was associated with RCT. With the description of a new risk factor, future research can be done to analyze how to prevent RCT or develop new treatment strategies since the disease's failure index is currently high. Level of evidence: II

Migraine is a multifactorial neurological disorder characterized by frequent moderate to severe intensity headaches. The genetic variations in synaptic and post-receptor signalling proteins have direct effect on the process of serotonergic neurotransmission. We aimed to investigate the genetic association of serotonin transporter (SERT) 5-hydroxytryptamine transporter-linked promoter region (5-HTTLPR) polymorphism and migraine risk in South-Indian population. A total of 304 subjects with migraine including with aura (MA) and without aura (MO) and 308 controls were included in the present study. The single nucleotide polymorphism (SNP) was detected using polymerase chain reaction (PCR) and confirmed by deoxyribonucleic acid (DNA) sequencing. The genotyping analysis revealed insignificant relationship with migraine subjects when compared with controls (P > 0.05). The minor ‘S’ allele showed no association with odds ratio (OR) = 1.23 [95% confidence interval (CI): 0.90-1.66], heterozygote with OR = 1.18 (95% CI: 0.82-1.69), and homozygote with OR = 1.51 (95% CI: 0.52-4.35). Further clinical studies are required to validate the results of SERT 5-HTTLPR promoter polymorphism in diverse ethnic descents especially in Asian populations.

Chronic periodontitis (CP) is characterized by an immune response, leading to the destruction of periodontal supporting tissue. The effect of inflammatory and genetic factors on periodontitis has been evaluated previously. The interleukin (IL‑17) as an inflammation regulator seems to play a critical role in periodontitis pathogenesis. Here, in the current study, we aimed to investigate the association of ‑197 G > A (rs2275913) IL‑17 gene promoter polymorphism with generalized severe CP in an Iranian population.

In this case–control study, a total of 54 patients with periodontitis and 118 normals were enrolled. The polymerase chain reaction‑restriction fragment length polymorphism technique was applied to detect IL‑17 promoter rs2275913 genotypes in association with the susceptibility to severe CP. Chi‑square test or Fisher’s exact test was employed to compare genotype frequencies between groups. P < 0.05 were considered statistically significant.

The distribution of genotypes and alleles was in Hardy–Weinberg equilibrium. Although no significant association was observed between the risk of periodontitis and genotype frequencies under any of the inheritance models, the GG genotype was higher in healthy controls, while the AG genotype was more frequently observed in patients under the codominant model ([odd ratio [OR] = 2.14, 95% confidence interval (CI) (1.01–4.53), P = 0.13]). The frequency of AG‑AA genotype was higher in patients under dominant inheritance model ([OR = 1.92, 95% CI (0.94–3.93), P = 0.068]), while GG‑AA and AG genotypes were higher in healthy controls under over dominant model (OR = 0.1.95, 95% CI [0.98‑3.86], P = 0.055).

The results of this study showed that the presence of allele A and AG genotypes could be considered possible factors in increasing the risk of developing CP, although the differences of allele and genotype frequencies were remarkable but not statistically significant between the two groups.

Genetics has been found to have a prominent role in autism and therefore pharmacogenetics may guide us to a better management of this disorder. Given the importance of Renin-Angiotensin System (RAS) in the function of the brain and its possible association with autism, genetic variations of RAS may influence response to autism treatment. In this study, 83 autistic children were enrolled (3 to 12 years of age). Degree of autism was confirmed by the DSM-V criteria and response to treatment was measured according to Aberrant Behavior Checklist (ABC) scale at baseline, at 4 and 12 weeks of risperidone therapy. Polymorphisms (ACE I/D, rs4343 and rs4291) were determined by PCR-RFLP. Our results indicate the positive role of long term therapy in autism (12 weeks vs 4 weeks). The highest response rate in ACE ID gene was in the DD genetic variant at both 4 and 12 weeks of treatment. For the ACE A2350G gene, all genetic variants did not respond well to treatment at 4 weeks, however at 12 weeks, positive response was dominant in the AG genetic variant. Highest response rate in the ACE A240T gene belonged to the AT variant at both 4 and 12 weeks of treatment. However, our results indicate no significant association between ACE gene polymorphisms and response to risperidone therapy in autistic children based on ABC scaling. In conclusion, this study does not support the hypothesis of involvement of RAS genetics in response to risperidone in autistic children.

This study aims to evaluate the catalytic activities of 31 CYP2C19 alleles and their effects on the metabolism of tapentadol in vitro. 

Insect microsomes expressing the CYP2C19 alleles were incubated with 50–1250 μM tapentadol for 40 min at 37 °C and terminated by cooling to -80 °C, immediately. Tapentadol and N-desmethyl tapentadol were analyzed by a UPLC-MS/MS system. The kinetic parameters Km, Vmax, and intrinsic clearance (Vmax/Km) of N-desmethyl tapentadol were determined. 

As a result, the intrinsic clearance (Vmax/Km) values of most variants were significantly altered, while CYP2C19.3 and 35FS had no detectable enzyme activity. Only one variant, N277K, showed no significant difference from CYP2C19.1B. Two variants CYP2C19.29 and L16F displayed markedly increased intrinsic clearance values of 302.22% and 199.97%, respectively; whereas 24 variants exhibited significantly decreased relative clearance ranging from 0.32% to 79.15% of CYP2C19.1B. Especially, CYP2C19.2G, 2H, R124Q, and R261W exhibited a drastic decrease in clearance (>80%) compared with wild-type CYP2C19.1B. 

As the first study of all aforementioned alleles for tapentadol metabolism, the comprehensive data in vitro may provide novel insights into the allele-specific and substrate-specific activity of CYP2C19.

Cardiovascular disease is one of the most common causes of morbidity and mortality worldwide. The Proline and Serine Rich Coiled-Coil 1 gene in 1p13.3 locus has been reported to be associated with low density lipoprotein cholesterol (LDL-C) and coronary artery disease (CAD). The objective of this study was to investigate the association between the rs599839 polymorphism of the Proline and Serine Rich Coiled-Coil 1 (PSRC1) gene with CVD outcomes in a population sample recruited as part of the Mashhad-Stroke and Heart-Atherosclerotic-Disorders (MASHAD) cohort.

Five hundred and nine individuals who had an average follow-up period of 10 years were enrolled as part of the MASHAD cohort. DNA was extracted and genotyped using the TaqMan-real-time-PCR based method.

The study found individuals with GA/GG genotypes were at a higher risk of CVDs (OR= 4.7; 95% CI, 2.5-8.7; p< 0.001) in comparison to those with AA genotype; however, the result was not significant for GG genotype data.

The results suggest that the GA/GG genotypes of the PSRC1gene locus were at increased risk of CVD in a representative population-based cohort, demonstrating further functional analysis to discover the value of emerging marker as a risk stratification biomarker to recognize high risk cases.